1. Field of the Invention
This invention is in the field of combinations of drugs for medicinal purposes, in particular, analgetic compositions for the treatment of pain and is more particularly concerned with the prevention of a particular type of drug abuse, i.e., the illicit use by parenteral administration of dosage forms intended for oral administration.
2. Description of the Prior Art
A. U.S. Pat. No. 3,254,088, which issued May 31, 1966, describes the preparation of naloxone and its activity as a narcotic antagonist.
B. U.S. Pat. No. 3,493,657, which issued Feb. 3, 1970, describes the combination of morphine and naloxone as a composition for parenteral use "which has a strong analgetic, as well as antagonistic effect, without the occurrence of undesired or dangerous side effects."
C. A New York Times article appearing in a July 14, 1970 issue describes the oral administration of naloxone to narcotic addicts as a method of treatment. The oral administration of naloxone (in high doses) "makes it impossible for the addict to experience a high no matter how much heroin he uses."
Applicants are of the opinion that the prior art neither teaches nor suggests that compositions of the instant invention can be effectively employed to overcome the problem of parenteral abuse of oral dosage formulations without diminishing or suppressing oral efficacy because such compositions are orally active as analgetic agents, but produce neither analgesia, euphoria, or physical dependence when administered parenterally.
Drug abuse has almost become a way of life to a rapidly growing segment of the world population, especially here in the United States. It has become the vogue of many of the younger generation to experiment with any type of drug that will produce an emotional, psychological, euphoric, depressive or generally psychodelic experience.
Those drugs most commonly employed for such illicit purposes include the barbiturates, lysergic acid diethylamide (LSD), mescaline, marijuana (tetrahydrocannabinol), strong analgetics (heroin, codeine, morphine, meperidine, propoxyphene [Darvon], methadone, dihydrocodeinone, pentazocine, and the like), the central nervous system stimulants (the amphetamines and the like) and some of the major and minor tranquilizers (the promazines, meprobamate, the diazepines, and the like). Most of these compounds are commonly used in medicine for the legitimate treatment of various conditions and therefore have a limited availability in our society. While these agents are a necessary part of modern medicine, it would be highly desirable (1) to produce new drugs that do not possess drug abuse potential or (2) to "denature" the old agents to prevent their illicit use. The pharmaceutical industry has been striving to achieve the first goal for many years but most regretably has only achieved very moderate success. If one focuses on the strong analgetics, it becomes apparent that much effort and money has been expended to produce chemicals possessing good analgetic activity but little or no addictive liability. While good progress has been made as evidenced, for example, by the development of propoxyphene as a replacement for codeine and pentazocine as a replacement for morphine or meperidine, it is unfortunate that these compounds are still reported in the medical literature to be addictive and/or euphoric and subjected to abuse by parenteral administration. Furthermore, some of these agents have undesirable side effects, i.e., bad hallucinations, etc.
It is commonly known to the narcotic enforcement agencies and others in the medical trades that a substantial amount of the strong analgetics destined for legitimate medicinal use are diverted to illicit use through dishonest or careless handling. In many instances, these drugs are obtained by the addict or potential addict by theft or casual prescribing practice by the physician.
It is known from experience that the true narcotic addict must feed his habit by the parenteral route (mainlining) to obtain the maximum euphoric effect. The potential addict or thrill-seeker will also experiment in the same manner. Unfortunately, a substantial amount of the legitimate strong analgetics formulated in oral dosage form are diverted to illicit parenteral use, i.e., the type of abuse with which this invention is concerned. Since the oral dosage forms of these drugs diverted from legitimate channels must be parenterally effective to produce the desired euphoria, it follows that if these oral dosage forms are in some way rendered inactive or unpleasant for parenteral use the addict or potential addict will be cut off from this particular supply of euphoretic drugs. Obviously, oral activity must be retained if a useful medicament is to be provided.
Naloxone, chemically known as 1-N-allyl-14-hydroxynordihydromorphinone (Merck Index, 8th Ed., p. 712, Merck and Co., Rahway, New Jersey; U.S. Pat. No. 3,254,088 [1966], is a potent narcotic antagonist when administered parenterally. This compound is useful for the treatment of narcotic overdosage or for the detection of addiction. However, while naloxone is extremely potent parenterally (a parenteral dose of 0.1 mg. to 2.5 mg. will produce narcotic withdrawal symptoms in the addict or have a narcotic reversal effect in an overdose situation), the compound must be administered orally in quantities 200 to 400 times greater to produce an equivalent effect. It is known that the contemporaneous parenteral administration of equivalent therapeutic doses of naloxone and an euphoretic narcotic or narcotic-like analgetic will negate the analgetic and euphoretic effect in the normal individual and the euphoric and/or maintenance effect of the analgetic in the addict.
Many interchangeable terms are commonly used to describe the psychic or physical dependence of people upon drugs. The term addiction is most commonly used when talking about the strong analgetics. The strong analgetics, in contrast to the weaker agents such as aspirin, acetaminophen, and the like, are employed in the relief of more severe pain. They usually produce a euphoric effect when taken parenterally. Orally there is usually no significant euphoria.
Addiction can develop to the barbiturates and strong analgetic agents, in the sense of the term "addiction" as defined by the Committee on Problems of Drug Dependence of The National Research Council, namely, a state of periodic or chronic intoxication, detrimental to the individual and to society, produced by the repeated administration of a drug, its characteristics are a compulsion to take the drug and to increase the dose, with the development of psychic and sometimes physical dependence on the effects of the drug, so that the development of means to continue the administration of the drug becomes an important motive in the addict's existence.
Addiction to narcotics or narcotic-like strong analgetics often occurs by the legitimate chronic parenteral administration of these agents in the alleviation of deep pain. More commonly, however, addiction to these agents occurs when the psychologically unbalanced or thrill-seeking individual looking for an escape from the realities of life finds his escape in the euphoria produced by the parenteral administration of strong analgetics. Euphoria is generally defined as a feeling of well-being. Euphoria can be produced in many ways, e.g., an exhilerating experience, alcohol, stimulants, depressants, narcotics, etc. For the purpose of this disclosure, "euphoria" is defined as an abnormal state of well-being produced by the parenteral administration of strong analgetics. The terms "euphoretic analgetics" and "strong analgetics," often called narcotic or narcotic-like analgetics, are also defined herein as including those chemical agents which upon parenteral administration are capable of maintaining or partially maintaining a known addict addicted to heroin or the like without substantial withdrawal symptoms. For the purpose of this disclosure, a "strong analgetic" can also be described as any analgetic agent whose analgetic, euphoric or dependence producing actions are negated by the parenteral administration of naloxone or a salt thereof.